Cspg4 high microglia contribute to microgliosis during neurodegeneration
Open accessAbstract
Microglia play a critical role in the pathogenic process of neurodegenerative diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD). Upon pathological stimulation, microglia are converted from a surveillant to an overactivated phenotype. However, the molecular characters of proliferating microglia and their contributions to the pathogenesis of neurodegeneration remain unclear. Here, we identify chondroitin sulfate proteoglycan 4 ( Cspg4, also known as neural/glial antigen 2)-expressing microglia as a specific subset of microglia with proliferative capability during neurodegeneration. We found that the percentage of Cspg4 + microglia was increased in mouse models of PD. The transcriptomic analysis of Cspg4 + microglia revealed that the subcluster Cspg4 high microglia displayed a unique transcriptomic signature, which was characterized by the enrichment of orthologous cell cycle genes and a lower expression of genes responsible for neuroinflammation and phagocytosis. Their gene signatures were also distinct from that of known disease-associated microglia. The proliferation of quiescent Cspg4 high microglia was evoked by pathological α-synuclein. Following the transplantation in the adult brain with the depletion of endogenous microglia, Cspg4 high microglia grafts showed higher survival rates than their Cspg4 − counterparts. Consistently, Cspg4 high microglia were detected in the brain of AD patients and displayed the expansion in animal models of AD. These findings suggest that Cspg4 high microglia are one of the origins of microgliosis during neurodegeneration and may open up a avenue for the treatment of neurodegenerative diseases.
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Cspg4-expressing microglia have the ability to proliferate triggered by pathological α-syn during neurodegeneration, particularly in PD.
“a specific type of microglia, known as Cspg4-expressing microglia, has been identified as having the ability to proliferate triggered by pathological α-syn during neurodegeneration, particularly in PD.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [219]
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Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets
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- Authors
- Liu, Y.-J., Ding, Y., Yin, Y.-Q., Xiao, H., Hu, G., & Zhou, J.-W.
- Affiliations
- Chinese Academy of Sciences (CN)
- Nanjing University of Chinese Medicine (CN)
- Institute of Neuroscience, State Key Laboratory of Neuroscience, Chinese Academy of Sciences (CAS) Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2023-02-16
- Volume
- 120
- Issue
- 8
- Pages
- e2210643120-e2210643120
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC9974490
- OpenAlex
- W4321002257
- Cited by
- 14
- References
- 60
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 6 · 2023: 2
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (U1801681)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- CSPG4, microglia, microglial activation, neurodegeneration, Parkinson's disease, Alzheimer's disease, microglial proliferation, cell cycle genes, alpha-synuclein, disease-associated microglia, microglial transcriptome, neuroinflammation
- MeSH terms
- Alzheimer Disease, Animals, Parkinson Disease, Phagocytosis, Microglia, Neurodegenerative Diseases, Mice
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